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Safety and efficacy of the thrombolytic agent pro-urokinase (pro-UK) in the treatment of deep vein thrombosis of the lower limbs (DVT) have been investigated in an open, uncontrolled, pilot study. Fifteen patients were infused with 800.000 IU (5 mg)/h of pro-UK over 24 h (120 mg), together with unfractionated heparin adjusted to maintain the activated partial thromboplastin time between 1.5 and 2.5 times the basal value. Efficacy was assessed comparing venographic changes in the 11 evaluable limbs before and after pro-UK infusion. The Marder score decreased from a median pre-thrombolysis value of 28 (range 4-40) to 16 (3-38) (p < 0.05). One major hemorrhagic event (retroperitoneal bleeding 4 days after the end of the pro-UK infusion) occurred. Fibrinogen, alpha 2-antiplasmin and plasminogen significantly decreased from baseline values after 12 and 24 h, fibrin(ogen) degradation products significantly increased. Changes in hemostasis parameters were unrelated to thrombolytic efficacy. The results of this pilot study indicate that pro-UK is thrombolytic in DVT and that it can be administered simultaneously with conventional heparin treatment.

In our Center for the Surveillance of Anticoagulant Treatment, most of the 1700 patients followed-up are traditionally treated with acenocoumarol, while warfarin is administered nowadays to an increasing proportion of patients. To assess if the difference in the pharmacokinetics of these two drugs may determine a different laboratory quality of treatment, a retrospective study was performed on the computerized files of all 142 patients on treatment with warfarin for more than 100 days and on a control group of 142 patients treated with acenocoumarol, matched for age, sex, disease state and duration of oral anticoagulant therapy (OAT). The study considered 7071 assays for a total of 432 patient-years of treatment. The overall quality of treatment was significantly better in patients treated with warfarin (72% of controls within the therapeutic range versus 67% on acenocoumarol, p < 0.001). Also the individual quality of therapy, which was assessed as the percentage of patients with 75% or more assays in range, was in favour of warfarin (50.7% vs 34.5%, p < 0.05). Warfarin therapy was more stable and fewer assays were required for treatment monitoring. Confounding factors possibly influencing the treatment stability, such as interfering drugs, diagnostic or therapeutical procedures requiring withdrawal of anticoagulation, were evaluated and no significant difference between the two groups was found. The difference in the laboratory quality of OAT was marked in patients treated for prevention of arterial thromboembolism, while it was negligible in patients with venous thromboembolic disease, whose mean duration of OAT was considerably shorter. Since there is no evidence that acenocoumarol is more efficacious or safer than warfarin, the latter seems to be preferable for patients who are candidate to very prolonged OAT.

In vitro and in vivo effects of adrenaline (ADR) on platelet aggregation, on platelet factor 3 (PF3) availability and on platelet factor 4 (PF4) release were studied in man. Inhibitory action of an alpha-blocker, phentolamine (PHEN) was investigated in the same conditions. The threshold concentration (TC) of ADR inducing the typical two-phase response in aggregation tests when added to platelet-rich plasma (PRP) varied in different pools of plasma, but always induced an evident PF4 release and increased PF3 availability. A further increase in both parameters was obtained with higher concentrations but without any significant dose/response correlation. Adding PHEN alone to PRP did not induce platelet aggregation or modify PF4 release induced by stirring, but it reduced PF3 availability. On the other hand, PHEN prevented the effects of ADR in different platelet tests, at appropriate concentrations. Intravenous infusion of ADR lowered the TC, and increased PF3 availability and PF4 release. In vivo administration of PHEN, in contrast, increased TC and reduced PF3 availability, while PF4 remained unchanged.